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Патент USA US3069326

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United States Patent O??ce
Patented Dec. 18, 1962
active against the ?agellate Hexamita salmonis, the causa
tive organism of hexamitosis in trout and salmon. The
previous known activity of fumagillin was against com
Gilbert Fred Otto, Lake Bluff, Ill., assignor to ‘Abbott
pletely unrelated protozoan organisms. It is effective
against one amoeba organism Entamoeba histolytica in
man, Nosema apis in bees but inactive against bacteria,
fungi, viruses andv other closely related protozoa. More
speci?cally, it has no activity against such pathogenic
?agellates as Trichomonas vaginalis, Trichomonas foetus,
Trypanosoma gambiense and Spirochoeta vovyi. Thus,
Laboratories, North Chicago, Ill., a corporation of
No Drawing. Filed June 19, 1961, Ser. No. 117,216
6 Claims. (Cl. 167-53)
This invention relates to a method and compositions
for the treatment of ?sh disease and more particularly,
it was most unexpected that fumagillin would be active
it relates to compositions containing fumagillin and a
against the related ?agellate, Hexamita salmonis.
method for employing the same to treat trout and salmon
Fumagillin is a well established antibiotic. It can be
infected with hexamitosis.
readily prepared as described in US. Patent 2,803,586
I-Iexamitosis is an enteric parasitic infection of trout 15 by fermenting Aspergillus fumigatus under submerged
and salmon. The causative organism is a ?agellate
aerobic conditions in a suitable nutrient medium and
known as Hexamita salmonis. With the inevitable crowd
isolating the fumagillin from the culture medium by
ing of young ?sh in hatcheries, there is ample opportunity
for massive exposure. Arti?cial conditions, including
extraction with a suitable solvent.
The method of treatment of the present invention in
arti?cial feed, create various stress factors which in 20 volves incorporating fumagillin in pelletized ?sh feed and
crease susceptibility to the infection. Mortality rates in
providing these medicated pellets of feed to ?sh naturally
hatcheries from the disease alone run as high as 50 to
infected with hexamitosis for limited periods of time.
75% in young fry or ?ngerlings and on occasion newly
in general, about 0.01 to 1.0% by weight of fumagillin
hatched trout have been completely wiped out. In the
in the diet is employed but about 0.2% by weight is
past, mercurous chloride or p-ureidobenzenearsonic acid 25 preferable from the standpoint of effectiveness, toxicity
have been employed in ?sh feed to treat the disease.
and palatability. The continuous feeding of from 0.001
However, neither of these remedies is dependable or
to about 0.002% by weight of fumagillin in the diet pro
vides a good prophylactic practice for preventing hexami
All species and varieties of trout and salmon appear to
tosis infection in healthy trout and salmon.
be susceptible to hexamitosis. It is usually evident as 30
In one test, fumagillin was incorporated in a concen~
chronic wasting disease, which runs its course in a matter
tration of 0.2% by weight into a commercial trout feed
of weeks accompanied by a high death rate. The ?sh
containing meat meal, ground corn, soybean oil meal,
fail to grow and lose weight. They are listless, often
?sh meal, dried buttermilk, brewer’s yeast and minor
lying on the bottom and occasionally make quick spastic
amounts of vitamins and essential minerals having an
movements from side to side. Upon microscopic exami
analysis of 56% protein, 4% fat and 5% ?ber. The
nation, ?agellates are found in the intestinal contents of
medicated feed was fed twice daily for ?ve days to 150
the sick ?sh. An acute outbreak of the disease may
salmon ?ngerlings naturally infected with hexamitosis.
become manifest only by the rapid death rate since 50%
All of the treated salmon were completely free of para~
or more of the ?sh die within 24 to 48 hours of the ?rst
sites at the end of the test period whereas the control
sign of the disease.
40 group which was untreated was heavily infested with
The problem of controlling hexamitosis is becoming
more serious since trout hatcheries are rapidly increasing
for the production of marketable ?sh and the stocking
of fee ?shing ponds as well as the increasing amount of
trout hatching by governmental agencies for stocking na
tional waters for sport ?shermen. There are now about
150 large hatcheries in the United States alone and many
smaller ones producing edible trout on a commercial
basis. The development of pelletized dry ?sh feed in the
past decade has accelerated the growth of the industry.
Not less than 30,000 tons of such feed is currently sold
annually ‘for trout and salmon raising. This market
should double by 1965 and increase ten fold by 1975.
As the trout industry grows, there will be increasing
numbers of problems of disease control of which the most
serious at present is hexamitosis. It would, therefore,
be bene?cial to develop methods and compositions which
are e?ective against this disease.
parasites of Hexamita salmonis.
In another test, fumagillin was fed to salmon infected
with hexamitosis in a concentration of 1.0% of the feed
as described above. Equally good results were obtained
in that the treated ?sh were devoid of the parasites within
5 days While the untreated control group was heavily
infested with parasites causing the disease.
In still other tests, the parasite causing hexamitosis
was completely eliminated from trout within 5 days or
less when the ?sh were fed fumagillin in amounts rang
ing from 0.01 to 0.04% by weight of their diet.
A direct comparative study of fumagillin with mer
curous chloride and p-ureidobenzenearsonic acid against
hexamitosis in salmon ?ngerlings revealed that only
fumagillin was effective in eliminating the infection at
0.2% by weight or less in the diet. There were no toxic
effects upon the host even at a concentration of 1% by
weight of the diet. In contrast, mercurous chloride was
It is the main object of this invention to provide a
completely inactive at 0.2% and toxic at 1.0% in the
method for the treatment of hexamitosis in trout and 60 diet whereas p-ureidobenzenearsonic acid was e?ective at
salmon. A further object is to provide compositions
containing fumagillin which are very effective in eradicat
ing hexamitosis in trout and salmon.
It has now been discovered that fumagillin is extremely
only 1% by weight in the diet. In similar tests, other
antibiotics such as erythromycin and chlorotetracycline
were ineffective against hexamitosis when employed at a
concentration of 0.2% by weight in the diet of salmon.
What I claim is:
1. A method‘ for treating salmon and trout to prevent
and control hexamitosis which comprises feeding said
?sh a composition containing fumagillin.
5. A ?sh feed useful for the control of hexamitosis
containing from 0.01 to 1% by weight of fumagillin.
6. In the practice of pisciculture, the method which
comprises feeding ?sh a solid composition containing
2. A method as claimed in claim 1 in which the 5 from 0.001 to about 0.002% by weight of fumagillin to
prevent hexamitosis.
fumagillin is mixed with a solid carrier.
3. A method as claimed in claim 1 in which the fuma
References Cited in the ?le of this patent
gillin is present in an amount of from about 0.1% to
1% by weight of the composition.
Lund: Yearbook of Agriculture 1956, pp. 444—446,
4. A method as claimed in claim 1 in which the fuma 10 US. G.P.O.
gillin is present in an amount of about 0.2% by weight
of the composition.
Hussar: Antibiotics and Antibiotic Therapy, 1954,
Macmillan C0., N.Y., pp. 377 and 378.
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